Fig. 1: Key interactions between cancer cells and the TME proposed in the model.

Cancer cell, , behaviour is dependent on the local concentration of the proliferation signal, , with thresholds for death, h_d, and proliferation, h_p. Cancer cells provide autocrine promotion of local proliferation signal at rate β. TME comprises of both passive, , and reactive stroma. Reactive stroma can be in either an activated, , or deactivated, , state. A targeted inhibitor drug, , depletes proliferation signal at rate δ and is removed from the system through vessel sites at rate μ. Local concentration of targeted drug above threshold h_r triggers activation of reactive stroma cells adjacent to a cancer cell, in turn providing paracrine promotion of the proliferation signal at rate γ. Activated reactive stroma reverts to a deactivated state if the drug concentration falls below h_r.